Rapidly disintegrating formulations are conventionally prepared by various methods using lyophilization, a disintegrating agent, a sublimation-like material, humidification or dehumidification.
For example, U.S. Pat. Nos. 5,631,023 and 5,976,577 disclose a formulation obtained by subjecting a drug-containing solution to lyophilization. Such formulations are recently employed in preparing products marketed by Merck, GlaxoWelcome, and Schering-Plough under the trade names of Pepcid™ RPD (a famotidine formulation), Zofran™ zydis (an ondansetron formulation), and Claritin™ RediTabs, respectively. These formulations disintegrate in the oral cavity within 2 to 3 seconds, but the process for preparing them requires the use of special equipments and packaging materials, causing reduced productivity and high manufacturing cost.
In order to solve this problem, International Patent Publication No. WO 99/47126 has suggested a method for preparing a formulation which is free from a residual organic solvent, by compressing an active ingredient together with a water-soluble polymer binder to form a tablet and subjecting the resulting tablet to humidification under a highly humid condition, followed by drying. This method is known as the WOWTAB technique developed by Yamanouchi Pharmaceuticals of Japan. In addition, International Patent Publication No. WO 93/12769 discloses a method for preparing a formulation by placing in a mold a suspension comprising an active ingredient, agar and sugar, and drying the suspension at 30° C. under a pressure of −760 mmHg. However, this method suffers from low productivity and nonuniform product quality.
Alternatively, the Orasolv technique for the preparation of a rapidly disintegrating formulation has been developed by Cima Labs, and disclosed in U.S. Pat. Nos. 5,178,878 and 6,024,981. The marketed product obtained by the Orasolv technique is represented by Zimig™ Rapimelt (a zolmitriptan formulation) marketed by Astrazeneka, but it does not undergo satisfactory oral disintegration and it gives an uncomfortable feeling when administered because of the generation of effervescent gases.
U.S. Pat. No. 3,885,026 teaches a method for preparing a porous tablet by mixing a volatile excipient such as urethane, urea, ammonium carbonate and naphthalene with other tablet components, compressing the mixture to form a tablet, and heating the tablet to remove the volatile excipient.
Further, U.S. Pat. No. 4,134,943 describes a method for preparing a porous tablet by mixing a solvent having a melting point ranging from −30 to 25° C. (e.g., water, cyclohexane, benzene, tert-butanol) with tablet components, cooling the mixture to solidify said solvent, compressing the solid mixture to form a tablet, and removing the solvent therefrom through evaporation. However, such porous tablets may be toxic due to the residual excipient or organic solvent.
As mentioned above, conventional rapidly disintegrating formulations are prepared by forming a tablet comprising a specific material removable by sublimation, evaporation or dehumidification, and then removing the corresponding specific material therefrom, so that they become porous and allow rapid penetration of saliva. However, such conventional formulations having deliberately formed pores suffer from significant deterioration of physical properties or undesired dimensional changes.
Therefore, there is need for developing rapidly disintegrating formulations capable of being easily manufactured and providing comfortable feeling to a patient during the administration without causing problems resulting from above mentioned conventional methods.